Adjuvant ipilimumab increases OS in high-risk melanoma
Ipilimumab, given as adjuvant therapy after complete resection of stage III melanoma, significantly improved overall survival (OS) and distant metastases-free survival (DMFS) vs placebo, according to new results from the EORTC 18071 trial. [ESMO 2016, abstract LBA2_PR]
The current report presents OS and DMFS data at a median follow up of 5.3 years. The phase III trial previously met its primary endpoint after 2.3 years, demonstrating a 25 percent improvement in recurrence-free survival (RFS) with ipilimumab, which led to its approval in the adjuvant setting in 2015. [Lancet Oncol 2015;16:522-530]
The investigators enrolled 951 treatment-naïve patients who underwent complete resection of stage IIIA, IIIB or IIIC cutaneous melanoma. Patients were randomized 1:1 to receive ipilimumab 10 mg/kg or placebo Q3W for four doses, then every 3 months for up to 3 years until completion, disease recurrence or unacceptable toxicity.
“Ipilimumab demonstrated a statistically and clinically significant improvement in OS. The 5-year survival rates were 65.4 vs 54.4 percent, representing a 28 reduction in mortality with ipilimumab vs placebo [p=0.001],” reported lead investigator Professor Alexander Eggermont of the Institut Gustave Roussy, Villejuif, France. “The OS benefit of ipilimumab was observed in all patient subgroups regardless of melanoma stage, number or type of positive lymph nodes, or ulceration.”
“There was also a 24 percent improvement in DMFS, with a median DMFS of 48.3 vs 27.5 months for ipilimumab vs placebo. In addition, our data confirmed the long-term RFS benefit of ipilimumab, with 5-year RFS rates of 41 vs 30 percent,” he added.
Treatment-related grade 3/4 adverse events (AEs) were much more common with ipilimumab vs placebo (45 vs 4 percent), and 32 percent of those led to discontinuation of the drug. “The most important grade 3/4 AEs were gastrointestinal [16 percent], hepatic [11 percent] and endocrine [8 percent]. Most were resolved within a month or two with established treatments, but endocrinopathies took much longer to resolve or required permanent hormonal replacement therapies,” he said. “There were no additional toxicities or deaths since the initial report at 2.3 years.”
Eggermont pointed out that ipilimumab had a much greater positive impact on OS in high-risk melanoma patients than interferon. [Eur J Cancer 2012;48:218-225]
“Adjuvant ipilimumab therapy provides a significant improvement in OS, and has a favourable risk-benefit ratio despite the marked immune-related AE rate,” he concluded. “Our data reinforce ipilimumab as an important treatment option for patients with high-risk stage III melanoma.”
“The final OS analysis shows for the first time that checkpoint blockade is effective in the adjuvant setting,” commented discussant Dr Olivier Michielin of the Lausanne University Hospital, Switzerland. “The benefit of ipilimumab appears to be more pronounced in patients with stage IIIC disease and multiple lymph-node involvement than those with less severe disease. Hence, treatment decision should factor clinical status and toxicity, and should be administered in experienced centres.”